Is Type 1 Diabetes Always Autoimmune?

Humoral Autoimmunity In Type 1 Diabetes: Prediction, Significance, And Detection Of Distinct Disease Subtypes

Humoral Autoimmunity in Type 1 Diabetes: Prediction, Significance, and Detection of Distinct Disease Subtypes 1Laboratory of Immunogenetics, The Brehm Center for Diabetes Research, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48105 2Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado 80045 Correspondence: George.Eisenbarth{at}ucdenver.edu Type 1 diabetes mellitus (T1D) is an autoimmune disease encompassing the T-cell-mediated destruction of pancreatic cells and the production of autoantibodies against islet proteins. In humoral autoimmunity in T1D, the detection of islet autoantibodies and the examination of their associations with genetic factors and cellular autoimmunity constitute major areas in both basic research and clinical practice. Although insulin is a key autoantigen and may be primus inter pares in importance among T1D autoantigens, an abundant body of research has also revealed other autoantigens associated with the disease process. Solid evidence indicates that autoantibodies against islet targets serve as key markers to enroll newly diagnosed T1D patients and their family members in intervention trials aimed at preventing or halting the disease process. The next challenge is perfecting mechanistic bioassays to be used as end points for disease amelioration following immunomodulatory therapies aimed at blocking immune-mediated -cell injury and, in turn, preserving -cell function in type 1 diabetes mellitus. A famous influential scientist of the past millennium, the Renaissance polymath Leonardo da Vinci (14521519), wrote: The supreme misfortune is when theory outstrips performance. This is a situation that perhaps shares some similarities with our knowledge on the path Continue reading >>

Type 1 Diabetes

Print Overview Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the pancreas produces little or no insulin. Insulin is a hormone needed to allow sugar (glucose) to enter cells to produce energy. Different factors, including genetics and some viruses, may contribute to type 1 diabetes. Although type 1 diabetes usually appears during childhood or adolescence, it can develop in adults. Despite active research, type 1 diabetes has no cure. Treatment focuses on managing blood sugar levels with insulin, diet and lifestyle to prevent complications. Symptoms Type 1 diabetes signs and symptoms can appear relatively suddenly and may include: Increased thirst Frequent urination Bed-wetting in children who previously didn't wet the bed during the night Extreme hunger Unintended weight loss Irritability and other mood changes Fatigue and weakness Blurred vision When to see a doctor Consult your doctor if you notice any of the above signs and symptoms in you or your child. Causes The exact cause of type 1 diabetes is unknown. Usually, the body's own immune system — which normally fights harmful bacteria and viruses — mistakenly destroys the insulin-producing (islet, or islets of Langerhans) cells in the pancreas. Other possible causes include: Genetics Exposure to viruses and other environmental factors The role of insulin Once a significant number of islet cells are destroyed, you'll produce little or no insulin. Insulin is a hormone that comes from a gland situated behind and below the stomach (pancreas). The pancreas secretes insulin into the bloodstream. Insulin circulates, allowing sugar to enter your cells. Insulin lowers the amount of sugar in your bloodstream. As your blood sugar level drops, so does the secre Continue reading >>

Autoimmune Aspects Of Type 2 Diabetes Mellitus - A Mini-review

Abstract Autoimmunity is a well-known pathogenic component in type 1 diabetes (T1DM). The assumption that the pathogenesis of type 2 diabetes (T2DM) also encompasses autoimmune aspects is recognized increasingly, based on the presence of circulating autoantibodies against β cells, self-reactive T cells, but also on the glucose-lowering efficacy of some immunomodulatory therapies in T2DM. The identification of these autoantibodies in elderly patients with slowly progressive manifestation of diabetes led to the introduction of a distinct clinical entity termed latent autoimmune diabetes of the adult (LADA), which combines features of both T1DM and T2DM. The autoantibody cluster differs in patients with LADA from patients with T1DM, but their presence indicates steady progression towards β-cell death and subsequent need for initiation of insulin treatment in a shorter period of time compared to autoantibody-negative T2DM patients. Autoimmune aspects in T2DM are not solely restricted to autoantibodies and thus LADA. They include the self-reactive T cells or defects in regulatory T cells (Tregs), which have been detected in autoantibody-negative T2DM patients as well. One contributor to the autoimmune activation in T2DM seems to be the chronic inflammatory state, characteristic of this disease. Upon inflammation-induced tissue destruction, cryptic ‘self' antigens can trigger an autoimmune response, which in turn accelerates β-cell death. Both innate and adaptive immune system components, specifically macrophages and self-reactive T cells, contribute to an increased secretion of inflammatory cytokines involved in inflammatory and autoimmune processes. However, the extent to which inflammation overlaps with autoimmunity is not known. Our review focuses on autoimmune invol Continue reading >>

Effect Of Associated Autoimmune Diseases On Type 1 Diabetes Mellitus Incidence And Metabolic Control In Children And Adolescents

Go to: 1. Introduction Diabetes is the most common chronic metabolic disease diagnosed in children and adolescents. Although it is not contagious, the disease is the first and only condition regarded by the United Nations as an epidemic of the 21st century [1]. In most parts of the world, type 1 diabetes is the most prevalent chronic disease in the population under 18 years of age although there are no reliable data available from many countries. There are significant differences in the incidence of the disease among different countries, with the lowest rates reported from China and Venezuela (0,1 per 100 000 people per year) and the highest in Finland and Sardinia (37 per 100 000 people per year) [2]. The results of international research (DIAMOND and EURODIAB) reveal an increasing trend in diabetes prevalence in most regions of the world, with the highest growth dynamics in the youngest age group [2]. The global increase in T1DM prevalence is a well-known fact; the incidence of type 1 diabetes in children worldwide has been growing at a rate from 3 to 5% per year since the 1960s, with the highest rate reported from fast developing countries [3–7]. The background of T1DM is probably associated with the autoimmune process of destruction of pancreatic beta cells by autoantibodies, which leads to absolute insulin deficiency and organ damage. However, there is no evidence that the destruction of the pancreatic beta cells is caused by the autoantibodies. The etiopathogenesis of this disease is complex and multifactorial. Most probably, the presence of many factors initiating or modulating the immune response leads to development of the disease [8]. As reported by literature, genetic factors have a crucial effect on the development of T1DM [9]. Genetic predisposition is re Continue reading >>

Associated Autoimmune Diseases In Children And Adolescents With Type 1 Diabetes Mellitus

INTRODUCTION Type 1 diabetes mellitus (T1DM), one of the most common chronic diseases in childhood, is caused by insulin deficiency resulting from the destruction of insulin-producing pancreatic beta cells. (See "Pathogenesis of type 1 diabetes mellitus".) Children and adolescents with T1DM are at increased risk for developing other autoimmune diseases, most commonly autoimmune thyroiditis and celiac disease. These associated autoimmune diseases are presented here. Other issues in this population are discussed separately: (See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents".) Continue reading >>

Autoimmune Diabetes Mellitus (type 1a) - Autoimmunity - Ncbi Bookshelf

Knip M. Disease-associated autoimmunity and prevention of insulindependent diabetes mellitus. Ann Med. 1997;29:447451. [ PubMed: 9453293 ] Cernea S, Herold KC. Drug insight: New immunomodulatory therapies in type 1 diabetes. Nat Clin Pract Endocrinol Metab. 2006;2:8998. [ PubMed: 16932263 ] Leslie RD, Atkinson MA, Notkins AL. Autoantigens IA-2 and GAD in type I (insulin-dependent) diabetes. Diabetologia. 1999;42:314. [ PubMed: 10027571 ] Carreras G, Mauricio D, Perez A, de Leiva A. Can all newly diagnosed subjects without type 1 diabetes-associated autoimmune markers be classified as type 1b diabetic patients? Diabetes Care. 2000;23:17151716. [ PubMed: 11092309 ] Decochez K, Tits J, Coolens JL, Van Gaal L, Krzentowski G, et al. The Belgian Diabetes Registry: High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. Diabetes Care. 2000;23:838844. [ PubMed: 10841006 ] Tiberti C, Buzzetti R, Anastasi E, Dotta F, Vasta M, et al. Autoantibody negative new onset type 1 diabetes lacking high risk HLA alleles in a Caucasian population: are these type 1b diabetes cases? Diabetes Metab Res Rev. 2000;16:814. [ PubMed: 10707033 ] Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of type 1 diabetes-the analysis of the data on published incidence trends. Diabetologia. 1999;42:13951403. [ PubMed: 10651256 ] Molbak AG, Christau B, Marner B, Borch-Johnsen K, Nerup J. Incidence of insulin-dependent diabetes mellitus in age groups over 30 years in Denmark. Diabet Med. 1994;11:650655. [ PubMed: 7955989 ] Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, La Porte R, Toumilehto J. Incidence of Childhood Type 1 Diabetes Worldwide. Diabetes Care. 2000;23:15161526. [ PubM Continue reading >>

Type 2 Diabetes: Is It An Autoimmune Disease?

For decades, doctors and researchers have believed type 2 diabetes is a metabolic disorder. This type of disorder occurs when your body’s natural chemical processes don’t work properly. New research suggests type 2 diabetes may actually be an autoimmune disease. If that’s the case, new treatments and preventive measures may be developed to treat this condition. Currently, there isn’t enough evidence to fully support this idea. For now, doctors will continue to prevent and treat type 2 diabetes with diet, lifestyle changes, medications, and injected insulin. Read on to learn more about the research that’s being done and the implications it may have on the treatment and prevention of type 2 diabetes. Type 2 diabetes has historically been viewed as a different type of disease from type 1 diabetes, despite their similar name. Type 2 diabetes occurs when your body becomes resistant to insulin or can’t produce enough insulin. Insulin is a hormone that moves glucose from your blood to your cells. Your cells convert glucose to energy. Without insulin, your cells can’t use glucose, and symptoms of diabetes can occur. These symptoms may include fatigue, increased hunger, increased thirst, and blurred vision. Type 1 diabetes, sometimes called juvenile diabetes because it’s often diagnosed in children and teens, is an autoimmune disease. In people with type 1 diabetes, the immune system mistakenly attacks the healthy tissues of the body and destroys the insulin-producing cells of the pancreas. The damage from these attacks prevents the pancreas from supplying insulin to the body. Without an adequate supply of insulin, cells can’t get the energy they need. Blood sugar levels rise, leading to symptoms such as frequent urination, increased thirst, and irritability. E Continue reading >>

Type 2: Autoimmune?

Conventional wisdom holds that Type 1 diabetes is an autoimmune condition — caused by a misguided attack by the immune system on the beta cells of the pancreas — while Type 2 diabetes is not, caused instead by a combination of genes and lifestyle. Experts have debated the relative importance of genes, lifestyle, and environmental factors in the development of Type 2 diabetes — and at times, studies linking Type 2 diabetes to pollution and toxins have fueled speculation that autoimmunity plays a role in its development. But until this month, there was little conclusive evidence of an autoimmune role in Type 2 diabetes. That changed last week, with the release of a study that addressed the potential connection between autoimmunity and Type 2 diabetes head-on. Published on the Web site of the journal Nature Medicine, the study had two components: one in humans, and one in mice. As described in a HealthDay article, for the mouse experiment, researchers fed mice a high-fat diet that would be expected to induce insulin resistance, a hallmark of Type 2 diabetes in humans. After five weeks, they gave some of the mice a drug, known as anti-CD20, that suppresses the immune system by depleting a type of immune system cell known as B cells. In mice given the drug, there was no sign of insulin resistance, and blood glucose levels were normal. All of the other mice developed insulin resistance. This result suggests that in overweight mice — and, most likely, humans — an immune system attack on fat cells, instigated by B cells, leads to insulin resistance. Conducting a similar experiment in humans would be much more complicated, both pragmatically and ethically, since the drug anti-CD20 (known as rituximab when intended for humans) broadly suppresses the immune system, not j Continue reading >>

Other Diseases That Are More Common In People With Type 1 Diabetes

Other Diseases That Are More Common in People With Type 1 Diabetes KidsHealth / For Parents / Other Diseases That Are More Common in People With Type 1 Diabetes Kids and teens with type 1 diabetes have a greater risk for other health problems, many of which also are autoimmune disorders. The diabeteshealth care team will watch kids for signs of these problems. But parents also should know what to look for so that they can alert doctors and get treatment, if necessary. In autoimmune disorders, the immune system attacks the body's healthy tissues as though they were foreign invaders. A severe attack can affect how that body part works. Type 1 diabetes is an autoimmune disease. The pancreas can't make insulin because the immune system attacks it and destroys the cells that produce insulin. Kids and teens with type 1 diabetes are at risk for other autoimmune problems, but these aren't actually caused by the diabetes. Doctors still aren't exactly sure why autoimmune diseases happen. But genetics probably play an important role because relatives of people with type 1 diabetes are more likely to have autoimmune diseases. Most kids with type 1 diabetes never need treatment for any other autoimmune disorder. But those who do might develop: These disorders can develop before a child is diagnosed with type 1 diabetes or months or years after the diabetes diagnosis. Kids and teens with type 1 diabetes are more likely to get disorders affecting the thyroid. The thyroid, which is part of the endocrine system , makes hormones that help control metabolism and growth. These hormones play a role in bone development, puberty, and many other body functions. Thyroid disease is fairly common in people with type 1 diabetes, affecting 15% to 20% of them. In thyroid disease, the thyroid gland Continue reading >>

Type 1 Diabetes With Other Autoimmune Diseases

Type 1 Diabetes With Other Autoimmune Diseases Editors Note: This content has been verified byMarina Basina, MD, a Clinical Associate Professor at Stanford University. Shes a clinical endocrinologist and researcher with a focus on diabetes management and diabetes technology. Dr. Basina is an active member of multiple medical advisory boards and community diabetes organizations, and she is on the Beyond Type 1 Science Advisory Council. People with Type 1 diabetes , an autoimmune disease, are more likely to have a co-occurring autoimmune disorder. An autoimmune disease means that your immune system sees your bodys own tissue as foreign invaders and attacks itself. For example, if you have Type 1, your body mistakenly attacks the insulin-producing (beta) cells in your body. The reason that co-occurring autoimmune disorders are so common isnt exactly known, although we do know that genetics play a significant role. Because we know that having Type 1 puts you at a higher risk of developing other autoimmune diseases, its important to be aware of what the signs and symptoms are. The following are warning signs that are common for all autoimmune diseases, including Type 1: These symptoms are non-specific and dont necessarily indicate another autoimmune disease. However, you should see your doctor if you are exhibiting them. Although the exact reason is unknown, there are a few autoimmune diseases that tend to co-occur with Type 1 diabetes that are listed below. 10% of the population with Type 1 diabetes also have celiac disease. Celiac disease is an autoimmune disease in which suffers are unable to eat gluten because it causes their bodys immune system to attack its own small intestine. If someone with celiac is undiagnosed and continues to eat gluten on a regular basis, the s Continue reading >>

Diabetes Overview

Almost everyone knows someone who has diabetes. An estimated 23.6 million people in the United States -- 7.8 percent of the population -- have diabetes, a serious, lifelong condition. Of those, 17.9 million have been diagnosed, and about 5.7 million people have not yet been diagnosed. Each year, about 1.6 million people aged 20 or older are diagnosed with diabetes. Diabetes is a disorder of metabolism -- the way our bodies use digested food for growth and energy. Most of the food we eat is broken down into glucose, the form of sugar in the blood. Glucose is the main source of fuel for the body. After digestion, glucose passes into the bloodstream, where it is used by cells for growth and energy. For glucose to get into cells, insulin must be present. Insulin is a hormone produced by the pancreas, a large gland behind the stomach. When we eat, the pancreas automatically produces the right amount of insulin to move glucose from blood into our cells. In people with diabetes, however, the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin that is produced. Glucose builds up in the blood, overflows into the urine, and passes out of the body. Thus, the body loses its main source of fuel even though the blood contains large amounts of sugar. The three main types of diabetes are Type 1 Diabetes Type 1 diabetes is an autoimmune disease. An autoimmune disease results when the body's system for fighting infection (the immune system) turns against a part of the body. In diabetes, the immune system attacks the insulin-producing beta cells in the pancreas and destroys them. The pancreas then produces little or no insulin. A person who has type 1 diabetes must take insulin daily to live. At present, scientists do not know exactly wh Continue reading >>

Are Obesity-related Insulin Resistance And Type 2 Diabetes Autoimmune Diseases?

Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases. Traditional autoimmune diseases involve a wide spectrum of clinical pathology and include diseases such as systemic lupus erythematosus, multiple sclerosis, Sjögren’s syndrome, rheumatoid arthritis, and type 1 diabetes. A disease is considered autoimmune if its pathology is dictated by a self-antigen–specific adaptive immune response. Immunologists have adapted Koch’s postulates, originally conceived to establish a causative link between microbes and infectious diseases, to define k Continue reading >>

What Causes Autoimmune Diabetes?

Autoimmune diabetes is influenced by genetics. What starts the autoimmune destruction is unknown, but it may be due to environmental factors. You may want to learn more about how type 1a diabetes develops. We know type 1a diabetes is caused by an autoimmune process in the body that mistakenly destroys the insulin-producing cells, or beta cells and occurs in genetically predisposed individuals. What starts the autoimmune destruction is unknown, but it may be due to environmental factors. In this section, you can learn more about: What is the Immune system? An overview of the different cells and organs in the immune system and how the immune system works Autoimmunity and diabetes: Current ideas about how the immune systems destroys insulin producing cells Continue reading >>

Type 1 Diabetes

Type 1 diabetes can occur at any age. It is most often diagnosed in children, adolescents, or young adults. Insulin is a hormone produced in the pancreas by special cells, called beta cells. The pancreas is below and behind the stomach. Insulin is needed to move blood sugar (glucose) into cells. Inside the cells, glucose is stored and later used for energy. With type 1 diabetes, beta cells produce little or no insulin. Without enough insulin, glucose builds up in the bloodstream instead of going into the cells. This buildup of glucose in the blood is called hyperglycemia. The body is unable to use the glucose for energy. This leads to the symptoms of type 1 diabetes. The exact cause of type 1 diabetes is unknown. Most likely, it is an autoimmune disorder. This is a condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue. With type 1 diabetes, an infection or another trigger causes the body to mistakenly attack the cells in the pancreas that make insulin. The tendency to develop autoimmune diseases, including type 1 diabetes, can be passed down through families. Continue reading >>

Type 1 Diabetes Causes

It isn’t entirely clear what triggers the development of type 1 diabetes. Researchers do know that genes play a role; there is an inherited susceptibility. However, something must set off the immune system, causing it to turn against itself and leading to the development of type 1 diabetes. Genes Play a Role in Type 1 Diabetes Some people cannot develop type 1 diabetes; that’s because they don’t have the genetic coding that researchers have linked to type 1 diabetes. Scientists have figured out that type 1 diabetes can develop in people who have a particular HLA complex. HLA stands for human leukocyte antigen, and antigens function is to trigger an immune response in the body. There are several HLA complexes that are associated with type 1 diabetes, and all of them are on chromosome 6. Different HLA complexes can lead to the development of other autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, or juvenile rheumatoid arthritis. Like those conditions, type 1 diabetes has to be triggered by something—usually a viral infection. What Can Trigger Type 1 Diabetes Here’s the whole process of what happens with a viral infection: When a virus invades the body, the immune system starts to produce antibodies that fight the infection. T cells are in charge of making the antibodies, and then they also help in fighting the virus. However, if the virus has some of the same antigens as the beta cells—the cells that make insulin in the pancreas—then the T cells can actually turn against the beta cells. The T cell products (antibodies) can destroy the beta cells, and once all the beta cells in your body have been destroyed, you can’t produce enough insulin. It takes a long time (usually several years) for the T cells to destroy the majority of th Continue reading >>